The long-term goal of this project is to identify the virus associated with LGL leukemia. This application represents a combination of classical and cutting edge approaches led by a multi-disciplinary team whose members are internationally recognized for their individual contributions to cancer research and mammalian genomics. We propose that LGL leukemia is caused by a novel retrovirus with similarities to both HTLV and HIV. We will use classical virology methods to isolate the LGL leukemia virus. We will test the hypothesis that the LGL virus can be transmitted from infected cells to target cells and identify optimum targets for high titer virus production. We will use state-of-the-art deep sequencing combined with whole genome analytical approaches to identify LGL leukemia viral sequences.